Claudin‐6 Protein Expression in Atypical Teratoid/Rhabdoid Tumors Is Strongly Enriched in the Molecular Subgroup AT/RT‐TYR

ABSTRACT Claudin‐6 has emerged as a promising immunotherapeutic target, yet protein‐level data in atypical teratoid/rhabdoid tumors (AT/RTs) have been inconsistent. We analyzed 36 well‐characterized AT/RT samples and found membranous claudin‐6 protein expression in 58% of cases, with striking enrichment in the molecular subgroup AT/RT‐TYR (100%) and significantly higher staining scores compared with AT/RT‐SHH and AT/RT‐MYC. Correspondingly, AT/RT‐TYR showed lower CLDN6 promoter methylation. Pilot spatial transcriptomic experiments in AT/RT‐TYR confirmed heterogeneous CLDN6 transcription, and co‐expression analyses linked CLDN6 to epithelial–mesenchymal transition‐related genes. These findings clarify subgroup‐specific expression patterns and support claudin‐6 as a biologically and therapeutically relevant target in AT/RT‐TYR.